POS0296 INTEGRATED SAFETY ANALYSIS OF TOFACITINIB IN ANKYLOSING SPONDYLITIS CLINICAL TRIALS
Authors: A. Deodhar, S. Akar, J. Curtis, B. Zorkany, M. Magrey, C. Wang, J. Wu, S. B. Makgoeng, I. Vranic, S. Menon, D. Fleishaker, A. Diehl, L. Fallon, A. Yndestad, R. B. M. Landewé
Journal: Annals of the Rheumatic Diseases (2022)

Background Tofacitinib is an oral JAK inhibitor for the treatment of adults with ankylosing spondylitis (AS). Objectives To describe the tofacitinib safety profile from an integrated analysis of randomised controlled trials (RCTs) in patients (pts) with active AS. Methods Pooled data from Phase (P)2 ( NCT01786668 ) and P3 ( NCT03502616 ) RCTs in pts with AS were analysed in 3 cohorts (Table 1): the 16-Week (Wk) placebo (PBO)-controlled cohort (pts receiving tofacitinib 5 mg twice daily [BID] or PBO from Wks 0–12 [P2 RCT] or Wks 0–16 [P3 RCT]), the 48-Wk all tofacitinib 5 mg BID cohort and the 48-Wk all tofacitinib cohort (pts receiving ≥1 dose of tofacitinib 2, 5 or 10 mg BID), including pts receiving tofacitinib from Wks 0–12 (P2 RCT) or Wks 0–48 (P3 RCT). Pts receiving tofacitinib 5 mg BID were included in the 16-Wk PBO-controlled cohort and both 48-Wk tofacitinib cohorts. Adverse event (AE)/AEs of special interest incidence rates (IRs; pts with events/100 pt-yrs) were reported based on a 28-day risk period (time of first to last study drug dose +28 days). Baseline (BL) cardiovascular (CV) risk was calculated post hoc by the atherosclerotic CV disease (ASCVD)-pooled cohort equations calculator for pts without history of coronary artery disease (48-Wk tofacitinib cohorts). Results At BL, most pts (&gt;76%) in the 48-Wk tofacitinib cohorts had &lt;5% (low) 10-yr ASCVD risk (Figure 1). The most common treatment-emergent AEs were nasopharyngitis/upper respiratory tract infection. Serious AE IRs were higher with tofacitinib 5 mg BID vs PBO in the 16-Wk PBO-controlled cohort, and similar in the 48-Wk tofacitinib cohorts (Table 1). Discontinuation due to AEs was similar between groups in the 16-Wk PBO-controlled cohort and between the 48-Wk tofacitinib cohorts (Table 1). One pt receiving tofacitinib 5 mg BID (included in the 16-Wk PBO-controlled and both 48-Wk tofacitinib cohorts) had a serious infection (SI; meningitis; Table 1). No SIs with PBO. Herpes zoster (HZ; all non-serious) occurred in the 48-Wk all tofacitinib 5 mg BID (5 pts [1.6%]) and 48-Wk all tofacitinib cohorts (7 pts [1.7%]; Table 1) only. Most cases involved a single dermatome, but 1 pt (tofacitinib 10 mg BID) had HZ involving 2 adjacent dermatomes. Across cohorts, there were no deaths or adjudicated opportunistic infections (OIs), OIs excluding tuberculosis (TB), TB, malignancies excluding non-melanoma skin cancer (NMSC), NMSC, major adverse CV events, thromboembolic events, gastrointestinal perforation or interstitial lung disease. Uveitis was reported in 1 (0.5%), 3 (1.6%), 4 (1.3%) and 6 (1.4%) pts in the tofacitinib 5 mg BID, PBO, 48-Wk all tofacitinib 5 mg BID and 48-Wk all tofacitinib groups, respectively; all but 1 pt (tofacitinib 2 mg BID) had history of uveitis. Psoriasis occurred in 1 (0.5%) pt (PBO) with history of psoriasis. There were no AEs of inflammatory bowel disease. Table 1. AEs and AEs of special interest 16-Wk PBO-controlled cohort 48-Wk tofacitinib cohorts Tofacitinib 5 mg BID N=185 PBO N=187 48-Wk all tofacitinib 5 mg BID N=316 48-Wk all tofacitinib N=420 AE, n (%), IR [95% CI per 100 pt-yrs] Serious AE 3 (1.6) 5.28 [0.00, 11.25] 2 (1.1) 3.56 [0.00, 8.49] 8 (2.5) 3.49 [1.51, 6.87] 9 (2.1) 3.45 [1.58, 6.55] Discontinuation due to AEs 4 (2.2) 7.04 [0.14, 13.94] 4 (2.1) 7.10 [0.14, 14.05] 11 (3.5) 4.77 [2.38, 8.54] 12 (2.9) 4.58 [2.37, 8.00] SI 1 (0.5) 1.77 [0.00, 5.89] 0 0.00 [0.00, 3.31] 1 (0.3) 0.43 [0.01, 2.41] 1 (0.2) 0.38 [0.01, 2.12] HZ 0 0.00 [0.00, 3.28] 0 0.00 [0.00, 3.31] 5 (1.6) 2.18 [0.71, 5.08] 7 (1.7) 2.68 [1.08, 5.53] All-cause mortality 0 0.00 [0.00, 3.28] 0 0.00 [0.00, 3.31] 0 0.00 [0.00, 1.59] 0 0.00 [0.00, 1.40] Malignancies excluding NMSC 0 0.00 [0.00, 3.28] 0 0.00 [0.00, 3.31] 0 0.00 [0.00, 1.59] 0 0.00 [0.00, 1.40] Major adverse CV event 0 0.00 [0.00, 3.28] 0 0.00 [0.00, 3.31] 0 0.00 [0.00, 1.59] 0 0.00 [0.00, 1.40] Venous thromboembolism 0 0.00 [0.00, 3.28] 0 0.00 [0.00, 3.31] 0 0.00 [0.00, 1.59] 0 0.00 [0.00, 1.40] CI, confidence interval; n, number of pts with event within 28-day risk period Conclusion Tofacitinib 5 mg BID was well tolerated over 48 Wks in pts with AS, and safety was consistent with the established safety profile of tofacitinib. Acknowledgements Study sponsored by Pfizer Inc. Medical writing support was provided by Jennifer Arnold, CMC Connect, and funded by Pfizer Inc. Disclosure of Interests Atul Deodhar Consultant of: AbbVie, Amgen, Aurinia, Boehringer Ingelheim, Bristol-Myers Squibb, Celegene, Eli Lilly, GlaxoSmithKline, Janssen, MoonLake, Novartis, Pfizer Inc and UCB, Grant/research support from: AbbVie, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer Inc and UCB, Servet Akar Speakers bureau: AbbVie, Amgen, Eli Lilly, MSD, Novartis, Pfizer Inc and UCB, Consultant of: AbbVie, Amgen, Eli Lilly, MSD, Novartis, Pfizer Inc and UCB, Grant/research support from: Pfizer Inc, Jeffrey Curtis Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, CorEvitas, LLC (formerly Corrona, LLC), Eli Lilly, Janssen, Myriad, Pfizer Inc, Radius, Roche and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, CorEvitas, LLC (formerly Corrona, LLC), Eli Lilly, Janssen, Myriad, Pfizer Inc, Radius, Roche and UCB, Bassel Zorkany Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Eva, Eli Lilly, Hekma, Janssen, MSD, New Bridge, Novartis, Pfizer Inc, Roche, Sanofi-Aventis and Servier, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Eva, Eli Lilly, Hekma, Janssen, MSD, New Bridge, Novartis, Pfizer Inc, Roche, Sanofi-Aventis and Servier, Marina Magrey Consultant of: AbbVie, Eli Lilly, Novartis, Pfizer Inc and UCB, Grant/research support from: AbbVie and UCB, Cunshan Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Joseph Wu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Solomon B Makgoeng Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Ivana Vranic Shareholder of: Pfizer Inc, Employee of: Pfizer Ltd, Sujatha Menon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Dona Fleishaker Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Annette Diehl Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Lara Fallon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Arne Yndestad Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Robert B.M. Landewé Consultant of: AbbVie, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Galapagos NV, Novartis, Pfizer Inc and UCB